Intranasal Insulin and Olanzapine Study in Healthy Volunteers

  • STATUS
    Recruiting
  • End date
    Oct 23, 2021
  • participants needed
    64
  • sponsor
    Centre for Addiction and Mental Health
Updated on 23 January 2021

Summary

Antipsychotic (AP) medications are considered to be the gold standard treatment for psychotic disorders including schizophrenia. However, APs have also been commonly associated with serious metabolic adverse effects including weight gain and Type 2 Diabetes, with younger populations disproportionately affected. In addition, young individuals treated with these agents have also been found to be at high risk for glucose dysregulation, including higher rates of prediabetes, with significant associations found between AP use and insulin resistance. Due to the concerning prevalence of these AP metabolic effects, it becomes important to further elucidate the mechanisms underlying AP effects on glucose metabolism, which are still poorly understood. One potential underlying mechanism is insulin which has been found to regulate hepatic (liver) glucose production through insulin receptors in the brain. These insulin receptors also play a role in neuronal growth and memory, or more broadly, cognition. Preliminary data in rat models has demonstrated that the AP olanzapine (OLA) inhibits the ability of a central insulin stimulus (acting at the level of the brain) to decrease endogenous glucose production (EGP), making this mechanism a prime target to translate from rodent models to human research. Furthermore, intranasal insulin (INI) administration (an analogous central insulin stimulus) has been repeatedly associated with improved cognitive performance for verbal memory and visuospatial functions in humans. Given these findings and with the goal of translational research, the present study will investigate OLA's effects in healthy human volunteers including: (a) the ability of INI to reduce EGP during a pancreatic euglycemic clamp (PEC; a glucose metabolism and insulin procedure); and (b) the ability of INI to improve cognitive performance. More specifically, the present study hypothesizes that:

  1. INI will be associated with a decrease in EGP relative to intranasal placebo (INP) as measured by the PEC. This effect will be inhibited if OLA is co-administered.
  2. OLA administration will be associated with decrements in cognitive measures (i.e., visuospatial, and verbal memory) as compared to placebo (PL). Additionally, OLA co-administration will block the beneficial effects of INI on cognition previously supported by other studies.
  3. INI will result in adaptive changes in neurochemical and neurohemodynamic measures as studied using MRI imaging techniques.

Description

The primary objective of the study is to examine whether a single dose of OLA given to young healthy volunteers during PECs can inhibit the activity of a central insulin stimulus (i.e, INI) to reduce endogenous glucose production. Secondarily, in an exploratory arm, this study seeks to examine whether a single dose of OLA can inhibit improvements associated with INI administration on specific cognitive domains (visuospatial, and verbal memory). Further, the study will also explore the effects of insulin and OLA on neurochemical and neurohemodynamic measures obtained through MRI imaging techniques.

To accomplish these objectives, this study will have two separate and parallel arms - a metabolic PEC arm to study the primary hypothesis, and an MRI imaging and cognitive testing arm to study the two secondary hypotheses.

Details
Condition Healthy Controls
Treatment Placebo, Saline, Insulin Lispro 100 UNT/ML, OLANZapine 2.5 MG
Clinical Study IdentifierNCT03741478
SponsorCentre for Addiction and Mental Health
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 17 yrs and 45 yrs?
Gender: Male or Female
Do you have Healthy Controls?
Do you have any of these conditions: Do you have Healthy Controls??
Healthy non-obese volunteers
Age: 17 to 45

Exclusion Criteria

History of current or past psychiatric illness (according to the Mini International Neuropsychiatric Interview [MINI])
Left-handedness (only for the cognitive and MRI arm)
Pre-diabetes or diabetes (fasting glucose 6.0mmol/L or use of anti-diabetic drug)
Evidence of impaired glucose tolerance on screening OGTT
Family history of diabetes
Use of weight reducing agents or other medications based on the discretion of the PI
History of liver disease or AST> 2 times upper limit of normal
History of kidney disease
Major medical or surgical event within the last 6 months
Any condition that interferes with safe acquisition of MRI data such as metal implants, pacemakers, cochlear implants, claustrophobia, etc. (only for the cognitive and MRI component)
Pregnancy and/or breastfeeding
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note